Interview with Brock Peters on stLFR, Perfect Genome, and WGS in Oncology
Brock Peters is Senior Director of Research at Complete Genomics, where he has worked for nearly 12 years. He earned his Ph.D. from Johns Hopkins University School of Medicine and previously contributed to cataloguing cancer gene mutations at Genentech. An expert in cancer genetics, Dr. Peters is enthusiastic about the power of whole-genome sequencing (WGS) to advance oncology by correlating mutation profiles with drug effectiveness.
Along with CSO Dr. Rade Drmanac, he has focused on enabling a “perfect genome” and recently introduced a technique called stLFR (single-tube long fragment read), which achieves affordable sequencing, haplotyping, and de novo assembly using unique co-barcoded second-generation sequencing reads. stLFR has already revealed genomic regions absent from reference genomes. Dr. Peters has used the technology to sequence a variety of genomes, including one very special subject — his dog, Jackson.
Q1. What first inspired your interest in genomic sequencing?
A: My graduate training was with Bert Vogelstein and Ken Kinzler, who were at the forefront of elucidating the genetic basis of cancer. Beyond that, they were excellent at developing technologies utilizing DNA. I developed a love for DNA engineering during my time in their lab and a strong belief that much human disease has a genetic basis. This naturally led to my desire to work on genome sequencing technology.
Q2. You have just introduced stLFR. How is this improving accuracy and cost-effectiveness?
A: Rade and I have been working to enable “Perfect Genome” sequencing — near error-free, reference-free sequencing and assembly. stLFR, combined with longer CoolMPS reads and advanced assembly algorithms from our partner Sentieon, helps achieve this goal. Assembling genomes without a reference is more cost-effective than aligning to one, particularly in a diploid fashion, making variant calling less computationally expensive and less error-prone.
Q3. You used stLFR on many genomes, even your dog Jackson’s. What did you discover?
A: Sequencing Jackson was partly for talks — people love seeing him. Unsurprisingly, parts of his genome are absent from the reference dog genome, similar to humans. Some of these extra sequences may fill gaps in the dog reference genome. Recreationally, Jackson has variants associated with agility and speed, which I can attest to. His mother is a purebred Dalmatian, though his father is a mix of several breeds, none Labrador, contrary to what we were told when adopting him.
Q4. How can stLFR help build better human reference genomes for diverse populations?
A: The genetics field is still defining what a reference genome means, given the variation across individuals. We initiated a project to gather, sequence, and catalog human variation across diverse ethnicities using stLFR. This data will be freely available to help the genetics community build better human reference genomes.
Q5. As an expert in cancer genetics, what advantages does WGS offer over traditional diagnostic tests?
A: For some cancer types, WGS currently offers no advantage. But for many others, it can place individuals on treatments that sometimes result in complete cures. Remarkably, tumors with certain mutation profiles respond to the same drugs even when located in different body regions, highlighting the importance of genetic background in cancer.
Q6. What significant advances can MGI’s technologies bring to research and people’s lives?
A: Simply put, vast improvement. The ultimate goal is better living through a deeper understanding of the genetics of life. Advances in sequencing accuracy, affordability, and throughput will expand research capabilities and improve clinical outcomes.
